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Starvation actively inhibits splicing of glucose-6-phosphate dehydrogenase mRNA via a bifunctional ESE/ESS element

T J Cyphert1, A L Suchanek, B N Griffith

  • 1Department of Biochemistry, West Virginia University, Morgantown, WV 26506, USA.

Biochimica Et Biophysica Acta
|May 2, 2013
PubMed

Insights

During starvation, heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds G6PD pre-mRNA, inhibiting splicing and reducing glucose-6-phosphate dehydrogenase (G6PD) expression. This nutrient-regulated splicing controls G6PD levels.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • Glucose-6-phosphate dehydrogenase (G6PD) expression is regulated post-transcriptionally.
  • Nutrient availability, particularly during starvation, impacts cellular metabolism and gene expression.

Purpose of the Study:

  • To investigate the molecular mechanisms regulating G6PD expression during starvation.
  • To identify the role of pre-mRNA splicing in G6PD regulation.
  • To determine the involvement of specific proteins in nutrient-regulated G6PD splicing.

Main Methods:

  • Analysis of G6PD pre-mRNA splicing rates under starvation conditions.
  • Identification and characterization of regulatory elements in G6PD pre-mRNA.
  • Investigation of heterogeneous nuclear ribonucleoprotein K (hnRNP K) binding to G6PD pre-mRNA.
  • Overexpression and siRNA-mediated depletion of hnRNP K.
  • Assessment of splicing factor SRSF3 interaction with G6PD pre-mRNA.

Main Results:

  • Starvation decreases G6PD mRNA levels by altering pre-mRNA splicing, specifically through intron retention.
  • A regulatory element in G6PD exon 12 binds hnRNP K.
  • hnRNP K expression increases during starvation and binds to G6PD pre-mRNA, inhibiting splicing.
  • hnRNP K binding to G6PD exon 12 blocks the splicing enhancer SRSF3.
  • Modulating hnRNP K levels directly impacts G6PD splicing and expression.

Conclusions:

  • hnRNP K acts as a nutrient-regulated splicing factor.
  • hnRNP K inhibits G6PD splicing during starvation by binding to a regulatory element in exon 12.
  • This mechanism provides a crucial link between nutrient status and G6PD expression control.
Keywords:
LiverNutrient regulationSRSF3hnRNP KmRNA splicing

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